Enzymatic degradation pattern of polysorbate 20 impacts interfacial properties of monoclonal antibody formulations
Author (Corporation)
Publication date
01/2024
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Course of study
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Type
01A - Journal article
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Parent work
European Journal of Pharmaceutics and Biopharmaceutics
Special issue
DOI of the original publication
Link
Series
Series number
Volume
194
Issue / Number
Pages / Duration
74-84
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
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Abstract
Polysorbate 20 (PS20) is widely used to maintain protein stability in biopharmaceutical formulations. However, PS20 is susceptible to hydrolytic degradation catalyzed by trace amounts of residual host cell proteins present in monoclonal antibody (mAb) formulations. The resulting loss of intact surfactant and the presence of PS20 degradation products, such as free fatty acids (FFAs), may impair protein stability. In this study, two hydrolytically-active immobilized lipases, which primarily targeted either monoester or higher-order ester species in PS20, were used to generate partially-degraded PS20. The impact of PS20 degradation pattern on critical micelle concentration (CMC), surface tension, interfacial rheology parameters and agitation protection was assessed. CMC was slightly increased upon monoester degradation, but significantly increased upon higher-order ester degradation. The PS20 degradation pattern also significantly impacted the dynamic surface tension of a mAb formulation, whereas changes in the equilibrium surface tension were mainly caused by the adsorption of FFAs onto the air-water interface. In an agitation protection study, monoester degradation resulted in the formation of soluble mAb aggregates and proteinaceous particles, suggesting that preferential degradation of PS20 monoester species can significantly impair mAb stability. Additional mAbs should be tested in the future to assess the impact of the protein format.
Keywords
Antibody aggregation, Fatty acids, Interfacial properties, Particles
Subject (DDC)
600 - Technik, Medizin, angewandte Wissenschaften
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ISBN
ISSN
0939-6411
1873-3441
1873-3441
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Hybrid
License
Citation
GREGORITZA, Kathrin, Christos THEODOROU, Marc HEITZ, Tobias GRAF, Oliver GERMERSHAUS und Manuel GREGORITZA, 2024. Enzymatic degradation pattern of polysorbate 20 impacts interfacial properties of monoclonal antibody formulations. European Journal of Pharmaceutics and Biopharmaceutics. Januar 2024. Bd. 194, S. 74–84. DOI 10.1016/j.ejpb.2023.11.024. Verfügbar unter: https://doi.org/10.26041/fhnw-11747